Design, synthesis, and biological activities of madindoline analogues

Bioorg Med Chem Lett. 2006 May 15;16(10):2807-11. doi: 10.1016/j.bmcl.2006.01.107. Epub 2006 Feb 14.

Abstract

A research program is under way to develop a series of madindoline-based inhibitors targeting interleukin 6. Such inhibitors will have potential use in fighting a variety of diseases for which no effective therapeutic drugs currently exist. Madindoline is no longer available from natural sources. Consequently, we have developed a purely synthetic route to ensure a supply of the compound. The synthesis of a range of analogues is described, all of which were evaluated for their inhibitory activity against the growth of IL-6-dependent 7TDI cells. From these assays, several synthetic madindoline analogues were identified as highly promising candidates for further development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Cell Line
  • Drug Design
  • Indoles / chemical synthesis*
  • Indoles / pharmacology*
  • Mice

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Indoles
  • madindoline A